This proposal requests partial support for a Gordon Research Conference (GRC) on The Biology of Post- Transcriptional Gene Regulation, to be held at Salve Regina University in Newport, Rhode Island, from July 18th to July 23rd, 2010. This GRC is the fourth of a series that has been held every other year since 2004. The broad and long-term goal of the Conference is to improve our current understanding of fundamental mechanisms and regulation of RNA biogenesis in normal and disease states. The emphasis is on post- transcriptional transactions involving the generation and metabolism of mRNA, but this extends to transcriptional coupling, and to factors involved in translation and its control, including tRNA and non-coding (e.g., micro) RNAs. The Specific Aims of this meeting will be to convene approximately 45 internationally known speakers representing key areas of post-transcriptional gene regulation, with a total of 150 participants, for a five-day meeting. The program will consist of nine morning or evening sessions that will broadly address cutting-edge issues in: coupling between transcription and RNA processing;genomics and evolution of RNA- processing signals and factors (including defining sites that are targets for RNA-binding proteins normally and in disease using immunoprecipitation followed by microarrays or high-throughput sequencing);RNA splicing catalysis, fidelity, regulation, and involvement in disease;RNA turnover, including nonsense-mediated mRNA decay;RNA transport and localization;non-coding RNA;translational control;and RNA-protein interactions. In addition, small poster sessions on four late afternoons will enable all participants to contribute to, and learn about, these topics. Free early-afternoon and late-evening periods in the relatively isolated summer setting of Salve Regina University will stimulate productive, informal discussions among established and junior principal investigators, post-doctoral trainees and graduate students from the U.S. and abroad. The significance of this application is that this GRC has a unique format and brings together sets of researchers who, despite having converging interests, have infrequent opportunities to meet as a group. The resulting discussions and cross- fertilization will help define critical areas to propel this field forward. In addition, elucidating the basic mechanisms of post-transcriptional gene regulation will be essential to gain a full understanding of the organization, function, and evolution of the human genome. The health relatedness of this application reflects the extensive involvement of RNA-processing dysfunction in numerous genetic diseases, neurological and neuromuscular disorders, and cancer. 1 PUBLIC HEALTH RELEVANCE: The relevance of this application to public health reflects the extensive involvement of defects in RNA metabolism associated with many human genetic diseases, neurological and neuromuscular disorders, and cancer. In addition, elucidating genomic networks as well as the basic mechanisms of the steps of gene regulation, which are the focus of this conference, will be essential to gain a full understanding of the organization, function, and evolution of the human genome.